Use of alkoxy-(tetrazol-1-yl)benzaldehyde compounds as pharmaceutical intermediates has been reported. For example, 2-methoxy-5-(5-methyltetrazol-1-yl)benzaldehyde is known to be of use as an important intermediate for a pharmaceutical that mainly serves as an analgesic or an anti-inflammatory agent (EP 0829480A2). Moreover, 2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)benzaldehyde is known to be of use as an important intermediate for a pharmaceutical that mainly serves as an analgesic (WO 96/29326).
Formylation reactions for aromatic compounds have been researched for a long period of time, and there are a variety of reported processes. Typical examples are (1) a process that uses dimethylformamide and phosphorus oxychloride (Org. Synth. Coll. Vol. 4, 1963, p. 539); (2) a process that uses dimethylformamide and trifluoromethanesulfonic anhydride (J. Chem. Soc., Chem. Commun., 1990, p. 1571); (3) a process that uses hexamethylenetetramine and trifluoroacetic acid (J. Org. Chem., vol. 37, 1972, p. 3972); (4) a process that uses imidazole and trifluoroacetic anhydride (Tetrahedron, vol. 36, 1980, p. 2505); (5) a process that uses carbon monoxide, hydrochloric acid and aluminium(III) chloride (Org. React., vol. 5, 1960, p. 290); and (6) a process that uses zinc(II) cyanide, hydrochloric acid and aluminium(III) chloride (Chem. Rev., vol. 63, 1963, p. 526).
However, when 1-(alkoxyphenyl)-1H-tetrazole compounds are subjected to formylation reactions according to processes (1) to (4) above, the reactions hardly progress. Processes (5) and (6) may be hazardous when used for commercial production because in process (5) toxic carbon monoxide is used, and in process (6) hydrogen cyanide is generated in the reaction system.
Therefore, formylation reactions for 1-(alkoxyphenyl)-1H-tetrazole compounds do not progress or are hazardous when prior-art processes are used. Prior-art processes are thus not industrially advantageous.